X-dibenzyloxy-x-nitrostyrenes



United States Patent 2,862,034 3,4-DIBENZYLOXY-p-NITROSTYRENES Kenneth E. Hamlin, Lake Bluff, [1]., assignor to Abbott fiaboratories, North Chicago, 111., a corporation of linois N0 Drawing. Application June 16, 1955 Serial No. 516,043

4 Claims, (Cl. 260-613) This invention relates to new chemical compounds of the 3-benzyloxy-B-nitrostyrene series characterized by the following structural formula.

wherein R is a member of the group consisting of hydrogen and lower alkyl, X is a member of the group consisting of hydrogen and nitro and Y is a member of the group consisting of hydrogen and benzyloxy, with the further proviso that X and Y cannot both be hydrogen in the same compound.

It is an object of this invention to provide novel chemical substances of the foregoing type and method for producing them. The compounds of this invention are especially useful as intermediates in the synthesis of medicinally active compounds.

The 3-benzyloXy-6,B-dinitrostyrenes of this invention can be cyclized according to the method disclosed by Beer .et .al. in Journal of Chemical Society, vol. 3 (1951) pages 2029-32, to form S-benzyloxyindoles. Indoles of this type can be converted to serotonin (S-hydroxytryptamine) by the method disclosed by Hamlin and Fischer in Journal of American Chemical Society, vol. 73, page 5007 (1951).

The 3,4-dibenzyloxy, fi-nitrostyrenes disclosed herein can be converted to 3,4-dihydroxy phenethylamines by the well-known reaction of reducing the ,B-nitrostyrene with lithium aluminum hydride (see Burger, Medicinal Chemistry, vol. 1, page 315). The phenethylamines are well-known sympathomimetic drugs as disclosed in Burger (supra) on page 294. The reaction of a fi-nitrostyrene to form a phenethylamine is likewise shown in Organic Reactions, vol. 6, page 482.

The new compounds are prepared generally by the reaction of a benzyloxybenzaldehyde with a nitroalkane such as nitromethane, nitroethane, nitropropane, or other lower nitroalkane, as set forth in detail in the examples. In a preferred process I have found that it is necessary to employ an excess of the nitroalkane which serves both as reactant and as solvent for the benzaldehyde derivative.

The invention is disclosed in further detail by means of the following examples which are set forth for the purpose of illustrating the invention but are in no way to be construed as limiting the invention in spirit or in scope. It will be apparent to chemists skilled in the art that many modifications in reagents and conditions can be adopted without departing from the intent and purpose of this invention, provided the modifications fall within the scope of the appended claims.

ice

Example I 3,4-dibenzy1oxy- 3-nitrostyrene (I)G Hg-CsHi O-C Hr-CaHs A solution of 35 g. (0.11 mole) of 3,4-dibenzyloxybenzaldehyde in 200 cc. of nitromethane is treated with 35 drops of n-arnylamine. After standing overnight, the resulting crystalline precipitate of 3,4-dibenzyloxy-18- nitrostyrene is filtered and recrystallized from methanol; yield 20 g., melting at 118-119 C.

Example 11 3,4-dibenzyloxy-p-methyLfl-nitrostyrene ?CH2-CaHa H O-GHr-CoHa tithe-CH,

A solution of 35 g. (0.11 mole) of 3,4-di-benzyloxybenzaldehyde in 200 cc. of nitroethane is treated with 35 drops of n-amylamine. After standing one week, the solution was permitted to evaporate to dryness. The residual crystalline 3,4-dibenzyloxy fl-methyl, El-nitrostyrene is recrystallized from ethanol and methanol; yield 38 g., melting at 117 C.

Example llI 3,4-dibenzy1oxy B-ethyLfl-nitrostyrene A solution of 50 g. (0.15 mole) of 3,4-dibenzyloxybenzaldehyde in 500 cc. of freshly distilled l-nitropropane is treated with 50 drops of n-arnylamine. After standing for one week, the solution is evaporated to dryness. The residual yellow crystalline mass is recrystallized from methanol and ethanol.' The resulting 3,4- dibenzyloxy ,B-ethyl, ,B-nitrostyrene is obtained in 89% yield (54 g.) and has a melting point of 107 C.

Example IV 3-benzyloxy-6,B-dinitrostyrene H O-GHz-CoHl H=CIJH A mixture of 11.5 g. (0.045 mole) of S-benzyloxy- 2-nitrobenzaldehyde, 7 cc. of nitromethane, 5 g. of ammonium acetate and 55 cc. of glacial acetic acid is refiuxed for two hours. The material is poured into water and the resulting solid is filtered, washed with water and 3 a dried. This solid, which is 3-benzyloxy-6,pdinitrosty- 3, pages 2029-32) and refluxed for ten minutes when a rene weighing 9 g., is recrystallized from diluted acetone precipitate is formed. A mixture of ethanol and water after treatment with decolorizing carbon; yield 6.4 g., is added to the reaction mixture and the whole is filtered. melting at 145-146" C." The filtrate is diluted with water, neutralized with sodium 5 bicarbonate and extracted with ether. The ether extracts Example V are dried and evaporated and the crystalline residue, 5- 3-:benzyloxy-6,;8-dinitrostyrene benzyloxyindole, weighing 0.8 g. is obtained. This prod- H V uct is converted to serotonin.

I This application is a continuation in part of my co- H pending application Serial No. 292,970, now abandoned,

which was filed June 11, 1952. NOV H Others may readily adapt the invention for use under various conditions of service, by employing one or more HZCH of the novel features disclosed or equivalents thereof. v 5 As at present advised with respect to the apparent scope of my invention, I desire to claim the following subject A solution of 26 g. (0.1 mole) of 5=benzyloxy-2-nitrott benzaldehyde in 150 cc. of nitromethane is treated with I l im; 26 drops of n-amylamine. After standing for 5 days, 1, A w compound of the general formula the mixture is evaporated to dryness and the resulting Y yellow crystals, of 3-benzyloxy 6,}9-dinitrostyrene weigh- 1 ing 20 g., are recrystallized from diluted acetone; yield 15 g., melting point 145-146 C. Ht"? (fO-CH2C5H3 H-C OH I Example VI 3,4-dlbenzyloxy-6,fi-dinrtrostyrene OCH2-COH5 OH=C' R N02 H wherein R is a member of the group consisting of hydro- NO gen and lower alkyl and Y is benzyloxy.

P 2. 3,4-dihenzyloxy-B-nitrostyrene.

I 3. 3,4-dibenzyloxy-B-methyl,B-nitrostyfene. CH=OH 4. 3,4-dibenzyloxy-/3ethyl,[3-nitrostyrene.

N02 A solution of 4.4 g. of 3,4-dibenzyloxy-6-nitrobenzal- References cued m the file of thls patent dehyde in 75 cc. of nitromethane is treated with 5 drops UNITED STATES PATENTS of D'PQY After Standing for Y? days, m 2, 01,2 2 Heinzelman J 24, 95 ture 1s evaporated to dryness The residual yellow crys- 2,698,345 Specter Dec 28, 1954 talline material 18 recrystallized from ethyl acetate to yield the desired 3,4-dibenzyloxy-6,,8-dinitrostyrene which 40 OTHER REFERENCES melts at 159460 Rosenmund: Berichte, vol. 46, pg. 1039 (1913).

Example VII Ginsberg: Chem. Abstracts, vol. 45, pgs. 625-6 (1951). 1 g. of 3-benzyloxy-6,fl-dinitrostyrene is mixed with 11 Fuson & Snyder: Orgamc Chemlstry; 2d John cc. of ethanol, 11 cc. of acetic acid and 3 g. of iron pow- Wiley & Sons (1954) der (Beer et al. Journal of Chemical Society (1951) vol. 

1. A NEW COMPOUND OF THE GENERAL FORMULA 